Altered sphingoid base profiles predict compromised membrane structure and permeability in atopic dermatitis

作者：Loiseau Nicolas; Obata Yasuko; Moradian Sam; Sano Hiromu; Yoshino Saeko; Aburai Kenichi; Takayama Kozo; Sakamoto Kazutami; Holleran Walter M; Elias Peter M; Uchida Yoshikazu^*

来源：Journal of Dermatological Science, 2013, 72(3): 296-303.

DOI：10.1016/j.jdermsci.2013.08.003

• Atopic dermatitis
• Barrier
• Ceramide
• Sphingosine

Background: Ceramide hydrolysis by ceramidase in the stratum corneum (SC) yields both sphingoid bases and free fatty acids (FFA). While FFA are key constituents of the lamellar bilayers that mediate the epidermal permeability barrier, whether sphingoid bases influence permeability barrier homeostasis remains unknown. Pertinently, alterations of lipid profile, including ceramide and ceramidase activities occur in atopic dermatitis (AD). %26lt;br%26gt;Object: We investigated alterations in sphingoid base levels and/or profiles (sphingosine to sphinganine ratio) in the SC of normal vs. AD mice, a model that faithfully replicates human AD, and then whether altered sphingoid base levels and/or profiles influence(s) membrane stability and/or structures. %26lt;br%26gt;Methods: Unilamellar vesicles (LV), incorporating the three major SC lipids (ceramides/FFA/cholesterol) and different ratios of sphingosine/sphinganine, encapsulating carboxyfluorescein, were used as the model of SC lipids. Membrane stability was measured as release of carboxyfluorescein. Thermal analysis of LV was conducted by differential scanning calorimetry (DSC). %26lt;br%26gt;Results: LV containing AD levels of sphingosine/sphinganine (AD-LV) displayed altered membrane permeability vs. normal-LV. DSC analyses revealed decreases in orthorhombic structures that form tightly packed lamellar structures in AD-LV. %26lt;br%26gt;Conclusion: Sphingoid base composition influences lamellar membrane architecture in SC, suggesting that altered sphingoid base profiles could contribute to the barrier abnormality in AD.

• 出版日期2013-12